Einfluss nicht‐konventioneller Medien auf die Carboligasereaktion ThDP‐abhängiger Enzyme

Gerhards, Tina; Lieres, Eric von; Wiechert, Wolfgang; Pohl, Martina; Gocke, Dörte

doi:10.1002/cite.201050096

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“…Solubility problems with benzaldehyde derivatives in aqueous media can be solved by adding water-miscible cosolvent, in this case dimethoxy sulfoxide (DMSO). 26,27 ■ RESULTS AND DISCUSSION Selection of a Suitable Carboligating Enzyme for the First Cascade Step. The enzymes with the highest selectivities and activities for the formation of (R)-and (S)-1 -h y d r o x y -1 -( 2 , 5 -d i m e t h o x y p h e n y l ) pr o p a n -2 -o n e (2,5DMPAC) were selected from the existing toolbox of ThDP-dependent enzymes.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The challenge of an unfavored equilibrium of the asymmetric transaminase reaction was solved by evaporating the coproduct acetone, shifting the equilibrium to the product side and increasing the overall cascade conversion. Solubility problems with benzaldehyde derivatives in aqueous media can be solved by adding water-miscible cosolvent, in this case dimethoxy sulfoxide (DMSO). , …”

Section: Introductionmentioning

confidence: 99%

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Methoxamine Synthesis in a Biocatalytic 1-Pot 2-Step Cascade Approach

et al. 2019

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Due to its function as a vasopressor, the vicinal amino alcohol methoxamine is a potential candidate for the treatment of hypotension and incontinence or has applications in ophthalmology. In this study, a biocatalytic method was developed to produce each of the four stereoisomers of methoxamine in a sequential 1-pot 2-step cascade reaction, starting from readily available pyruvate and 2,5-dimethoxybenzaldehyde without intermediate isolation. All four isomers are accessible with high conversions and very good stereoselectivities through the modular combination of carboligases and transaminases with high stereoselectivities. The development of these cascades was made possible, among other factors, by the integration of a recently engineered triple variant of the pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G-I468A-W543F), which provided access to the intermediate (S)-1-hydroxy-1-(2,5-dimethoxyphenyl)propan-2-one with a high enantiomeric excess of 98%. For the amination of these sterically demanding 2-hydroxy ketones, Bacillus megaterium transaminase in particular has proven to be a highly active and selective catalyst. All four methoxamine stereoisomers were achieved with isomeric contents between 94% and 99% and total conversions of both steps between 59% and 80%. Separation of each isomer without derivatizing was possible using supercritical fluid chomratographie with two columns connected in a row. A preparative scale (75 mL) of the 1-pot 2-step cascade to (1S,2R)-methoxamine including nonoptimized product isolation showed 85 mg HCl salt (46% isolated yield) with 94% purity (NMR) and an isomeric content of 98%.

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Section: ■ Introductionmentioning

confidence: 99%